My long-term research goal is to understand the principle factors responsible for bone fragility and determine how interventions can be maximized to strengthen the skeleton. Currently, the main focus of my research is to better understand the effects of bisphosphonates on bone remodeling, osteocyte viability, and matrix necrosis in bones of the oral cavity.
The overall goal of the research performed in my laboratory is to understand the mechanisms by which osteocytes, the most abundant bone cells, control the work of bone forming osteoblasts and bone resorbing osteoclasts, in response to hormonal and mechanical stimuli.
Ten million people in the US suffer from osteoporosis, a disease of reduced bone mass and debilitating fractures. Teriparatide (parathyroid hormone, PTH) is the only FDA-approved drug that replaces bone lost to osteoporosis. However, it is not the drug of first choice primarily due to cost. A cost-effective strategy for delivering teriparatide should include developing shorter courses of treatment that yield similar efficacy as longer-term therapy. Moreover, this might alleviate concerns over tachyphylaxis, where extended use of PTH results in diminished benefits.
Research in my laboratory is centered on identifying how microglia, the resident innate immune cells in the brain, can become a chronic source of cytokines and reactive oxygen species that drive progressive neuron damage. More specifically, we strive to identify the triggers (environmental and endogenous disease processes) that initiate deleterious microglial activation, reveal the underlying mechanisms, and apply these findings toward the development of markers of ongoing silent neuropathology and therapeutic strategies capable of halting the progression of central nervous system (CNS) diseases/damage. While the major focus of our studies is on Parkinson’s disease, Gulf War Illness, and Alzheimer’s disease, our research indicates that many of the molecular and environmental mechanisms we are actively pursuing may impact the persistent nature of chronic neuron damage in diverse CNS conditions/diseases.
Dr. Bonewald’s research focuses on the biology and function of the osteocyte. At present there are two major focus areas, the first is on crosstalk between osteocyte and muscle. Muscle secretes factors that maintain osteocyte viability and function and conversely osteocytes produce factors that support myogenesis and muscle function. These factors are being identified and their functions characterized. A second focus of the lab is the role of the osteocyte in calcium homeostasis under calcium demanding conditions such as during pregnancy. The mechanisms by which osteocytes can remove and replace calcium in their microenvironment is being examined. Trainees can learn osteocyte and muscle cell culture, isolation of primary osteocytes and muscle satellite cells, muscle contractility, application of fluid flow shear stress, mitochondrial imaging, loading and unloading of transgenic animals, in addition to standard molecular approaches and analyses.
There is a growing recognition that medical education should be evaluated with the same rigor as biomedical science if we are to produce better health care providers. My current scholarly work is concentrated in two areas: The evaluation of curricular innovations in medical education and the development of graduate degree programs to train the next generation of anatomy teachers and educational researchers.
Dr. Burr's current research activities include evaluation of the effects of pharmacologic agents used to treat osteoporosis on properties associated with quality of the bone matrix, specifically, the accumulation and repair of microdamage, changes in mineralization and alterations to the collagenous matrix.
Anatomical and neuroanatomical correlates of function and/or behavior – fMRI/brain activation patterns during bruxing, masticatory biomechanics; neurophysiology of mastication; function/dysfunction of temporomandibular joint; interaction between central pattern generators in CNS and morphology of the craniofacial complex; neurotransmitter stimulation and inhibition of brainstem motoneurons and their morphological sequelae in the craniofacial complex.
I have two main areas of research interest. The first area involves the structure and functional changes observed when blood vessels grow and remodel in disease states. The second area involves understanding kidney structure and function in disease states such as diabetes, hypertension, and in models of renal injury. Current research involves understanding the injury created by shock wave lithotripsy treatment. Shock wave lithotripsy (SWL) is used to fracture kidney stones. It is an effective treatment for most small stones and is widely used throughout the world.
As a paleoanthropologist, my research addresses questions related to ape and human evolution. Specifically, I am interested in the functional relationships between the mechanical loading associated with dietary and locomotor adaptations and hard and soft tissue anatomy, and what these relationships might reveal about the paleoebiology and evolution of fossil apes and early humans. The more accurate our interpretations of fossil ape and early human locomotor adaptations and diet, the greater the potential for that information to contribute answers to research questions about why these taxa evolved, what made them successful in some cases, and extinct in others, and the connection between diet and locomotion and the origins of the lineages of living apes and humans.
My research interests focus on the physiological and pathophysiological role of osteocytes in the regulation of skeletal remodeling. In particular, I am interested in the role that these cells play in the progression of multiple myeloma and its associated musculoskeletal disease.
My research interests have dealt primarily with structural/functional relationships of the kidney during the process of nephrogenesis and injury (acute and chronic). Qualitative and quantitative studies have been performed on the developing proximal tubules and collecting ducts. Abnormal developmental processes are being investigated in models of human polycystic kidney disease.
Kidney stone disease and therapies (including shock-wave lithoptripsy and percutaneous nephrolithotomy); noninvasive imaging of regional kidney function and structure; biology of novel and classical angiotensin receptor systems in the kidney.
My lab is interested in understanding the organization and plasticity of neural circuits in the cerebral cortex, and the mechanisms of epileptogenesis following traumatic brain injury. These topics are investigated with a variety of techniques at molecular, cellular and circuit levels, including laser scanning photostimulation combined with whole cell patch clamp recording, organotypic brain slice culture, gene gun transfection, time lapse confocal imaging, in vitro and in vivo optogenetic stimulation.
My overall career goal is to integrate preclinical and clinical research to investigate the mechanisms of centrally regulated anxiety and panic-associated behavior that coincides with cardio-respiratory and thermoregulatory activity, and determine how these systems contribute to menopausal symptoms (e.g., hot flashes and anxiety) from loss of estrogen tone; neuropsychiatric disorders such as panic disorder and post traumatic stress disorder (PTSD); and respiratory disorders such as chronic obstructive pulmonary disorder (COPD).
My research goal is to understand the relationship between skeletal muscle and bone to maintain the homeostasis of musculoskeletal system. My current research focus is to understand the effect of contracted muscle derived factors on bone metabolism as well as osteocyte viability/function.
CDNA cloning, in situ hybridization, immunocytochemical localization, quantitation, characterization, metabolism, and receptor activity of hypothalamic and extra hypothalamic neuroactive peptides and their effects on neuroendocrine function, neurologic and affective disorders and epilepsy. Specific peptides under investigation are thyrotropin-releasing hormone (TRH), Gonadotropin-releasing hormone (GnRH), Beta-endorphin and leucine enkephalin with major emphasis on TRH.
The goal of my research is to understand the molecular mechanisms underlying neuronal death and dysfunctions after brain injury. My current research project is investigating the change of ion channel in ischemic stroke and traumatic brain injury.
We work in the field of kidney stone disease and our laboratory is part of a collaborative effort investigating the origin, diagnosis and treatment of renal stones. The main focus of the lab is in lithotripsy research, where we are working to understand the mechanisms of shock wave action involved in the breakage of stones, how shock waves lead to the tissue trauma that accompanies lithotripsy, and how to make lithotripsy safer and more effective.
Basic science research interests revolve around bone and joint pathology. The McNulty lab uses both advanced imaging (e.g. micro-computed tomography) and histological techniques to evaluate changes in bones and joints secondary to various diseases and treatments.
The overall Aim of my research program is to understand the biological mechanisms of mechanical adaptation of bone and muscle. The current focus of my lab is on the relationship between bone and muscle mechanics at the whole-organ level, and how adaptations of tissue-level morphology influence whole-organ function. This is being investigated through three main studies: 1) pharmacological interventions to improve bone and muscle quality in a rat model of chronic kidney disease; 2) combining FDA-approved anti-osteoporosis drugs to maximize bone quality over monotherapy; and 3) effect of altered mechanical loading environment on the mechanical properties of the growing and adult musculoskeletal system.
The goal of my research is to understand the molecular mechanisms that are involved in the regulation of intracellular signaling in bone cells. In particular, my research focuses on the role of connexin43 as a regulator of intracellular signaling activated by pharmacotherapeutic, hormonal and mechanical stimuli in cultured cells and in animal models.
My laboratory works on treatments for metabolic and genetic bone diseases. We use molecular genetic approaches in rodents to identify new ways to make bone stronger. One particular approach that we have focused on is mechanobiology. Mechanobiology merges the older science of mechanics with the newer and emerging disciplines of molecular biology and genetics.
My laboratory is interested in understanding the role of the calcium/calmodulin dependent protein kinase (CaMK) signaling cascade in cell biology and how its alterations contribute to disease. We use global and conditional knockout mouse models to investigate the mechanisms by which one of the upstream kinases in the CaMK cascade, CaMKK2 along with its downstream kinases CaMKI and CaMKIV, as well as targets regulate the fate and function of bone marrow-derived mesenchymal stem cells, osteoblasts and osteoclasts. Functional outcome of the manipulation of the CaMK cascade in age and cancer-associated osteoporosis is a special focus.
My research interests are in skeletal biology and include studies on how lipids, particularly omega-6 and omega-3 fatty acids, and flavenoids affect bone modeling and remodeling in normal and estrogen-deficiency conditions. I am also involved in studies utilizing rodent models of chronic renal disease to understand the pathophysiology of bone loss and vascular calcification during renal failure and how these conditions can be treated pharmacologically.
My research interests are in PTHrP and neuropeptides, and uterine smooth muscle include studies on localization, effect and mechanism of action. I am also involved in studies involving education of basic science teaching.
My overall research objective is to understand the neural circuitry that regulates anxiety and how manipulations of this circuit leads to pathological anxiety and panic. It is my hope that findings from these types of experiments will lead to novel treatments for anxiety and panic disorders. My lab utilizes behavioral pharmacology coupled with neuranatomy and molecular biology to elucidate the functional circuits of anxiety behaviors.
Kidney stones affect a large number of Americans, with about 12% of people having at least one stone in their lifetime, and half of these people will have more than one stone. Stones are rarely life-threatening, but they cause intense pain and often require surgical procedures to be removed. The causes of kidney stones are not fully understood, but it is obvious that the causes are many, and thus the treatments for stones will also be diverse.
A central interest of our research is to understand how the brain processes complex sounds in generating auditory perception. Extracellular single-unit recording is used to analyze the functional organization of the mammalian auditory cortex. Neuroanatomical tract-tracing is employed to determine the anatomical connections of physiologically-identified regions. A computational neuroscience approach is further used to model single neurons with artificial neural-networks and signal-processing techniques.
Our research focuses on the pathogenesis of neuronal injury after cerebral ischemia or traumatic brain injury using in vivo and in vitro preparations. The alterations of synaptic transmission and ion channels after the insult and their roles in neuronal damage/survival will be studied using electrophysiological, morphological and molecular biological approaches. We also collaborate with other investigators on pain and spinal cord injury researches.
My long-term research interests include the area of neural development and neural plasticity of the brain as well as related dysfunctions and diseases. In recent years, my team has focused on the neural program during development and its reprogramming responses to environmental inputs at a mature stage. We believe our brain is precisely shaped through a, intrinsic, yet-to-be explored, genetic-cellular expression that is orchestrated further upstream by an epigenetic program. This program can be influenced by environmental inputs such as alcohol and drugs.